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Cell Rep. 2016 Nov 22;17(9):2286-2298. doi: 10.1016/j.celrep.2016.10.080.

LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.

Author information

1
Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA.
2
Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology & Biochemistry at UCI, Irvine, CA 92697, USA.
3
Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
4
Institute of Stem Cell Biology and Regenerative Medicine and Ludwig Center, Stanford University, Stanford, CA 94305, USA.
5
Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. Electronic address: hmikkola@mcdb.ucla.edu.

Abstract

The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1-/- concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization.

KEYWORDS:

LYVE1; definitive hematopoiesis; fetal liver; hemogenic endothelium; lineage tracing; primitive hematopoiesis; yolk sac

PMID:
27880904
DOI:
10.1016/j.celrep.2016.10.080
[Indexed for MEDLINE]
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